Primate Parkinson's Treatment Reveals New Side of Stem Cells

Share

Primate Parkinson's Treatment Reveals New Side of Stem Cells

In figure A, the white arrow indicates where neural stem cells were injected into a monkey’s brain and the green dots represent the stem cells’ migration.

Figure B highlights the area enlarged in figure C indicating where stem cells are located.

The green dots in figure D represent stem cells clustered in the ventral mesencephalon, a center of dopamine production.

Stem cells work in mysterious ways.

That's the tantalizing finding from scientists who treated monkeys with Parkinson's disease using fetal stem cells.

Their results mark the first successful stem cell therapy for Parkinson's in primates. The big news, however, is not simply that the treatment worked, but how it worked: by rescuing and rejuvenating, rather than replacing, diseased cells.

"It's a different principle of stem cell action from what everyone's thinking about," said Richard Sidman, a Harvard Medical School neuroscientist and co-author of the research.

The study is a landmark, both for treating Parkinson's disease and for highlighting a new therapeutic approach to stem cells. While most scientists are struggling to change stem cells into the types of cells they need – neurons, insulin-producing cells, heart cells, etc. – the new work shows that stem cells can perform the remarkable task of saving damaged cells.

The findings, which will soon be published in the Proceedings of the National Academy of Sciences, show that neural stem cells have "therapeutic mechanisms other than replacement," said Cesar Borlongan, a Medical College of Georgia neurologist. Borlongan said he has observed similar effects when using stem cells to treat Parkinson's symptoms in rodents.

The mechanism could provide an alternative to the tricky prospect of coaxing stem cells to take on specific functions, a process known as differentiation, and then meld seamlessly with the brain, Sidman said.

"It's a lot nicer to protect a patient's own cells, because those cells are already in the brain and are wired to work the way the brain is supposed to work," Sidman said. "If you put in differentiated cells, you have to get them to connect with the other neurons and make a functional circuitry."

Rewiring the brain with new cells is indeed "devilishly difficult," said Bill Langston, founder and scientific director of The Parkinson's Institute, a research foundation. But he's less sanguine about injecting patients with undifferentiated cells and trusting Mother Nature to take care of the details.

"It's not as controlled a directive as we'd like in the clinic," he said. "But these results are going to spur the field forward."

Sidman, along with Yale University's Eugene Redmond and Evan Snyder of the Burnham Institute for Medical Research, injected stem cells taken from the brains of 13-week-old aborted human fetuses into African green monkeys with damaged dopamine-producing brain cells.

Dopamine is a neurotransmitter that affects motion and balance. The death of so-called dopaminergic neurons has been linked to Parkinson's disease, an incurable neurodegenerative disorder that affects about one million Americans.

At the time of the injections, the monkeys couldn't feed themselves or walk without assistance, and alternated between periods of absolute stillness and uncontrollable tremors. Two months after the treatment, they were able to walk and eat. The tremors had disappeared.

"The behavioral improvement was very impressive," Langston said.

Four months after the injection, the effects started to wear off. Sidman's team sacrificed the monkeys and looked into their brains to see what had happened.

They figured the stem cells, which when injected were on their way to becoming different types of brain cells but hadn't yet specialized, would replace the monkey's own neurons. That's how stem cells are expected to work.

But far from turning into a mass of brand-new dopamine-producing neurons, most of the cells clustered around existing neurons, protecting them from further damage and rejuvenating those that had deteriorated.

Exactly how the injected cells restored the dying cells to life isn't clear. They probably secreted a cocktail of neuron-replenishing chemicals, but the exact recipe needs to be determined.

Borlongan says the study suggests that stem cells might someday be effective against Parkinson's if injected at an early stage of the disease, when there are still dopaminergic neurons to save.

But Sidman cautions that clinical trials in people are still far away, as the procedure's long-term risks aren't known and the method is still being refined.

The transplants' declining effectiveness over time may also indicate that the monkeys' immune systems rejected them. That would require transplant recipients to take immunosuppressant drugs – but in a medical catch-22, the drugs could prevent the stem cells from working.

"We think this protection is a new principle of some greater generality," Sidman said. "I'm not saying it would apply in all diseases, but it could apply to more than Parkinson's disease. It might not be a clinical treatment tomorrow morning – but it's a meaningful step."